β-酮磺酰胺腺苷酸化抑制剂作为潜在抗结核药物的设计、合成及生物学评价
Design, synthesis, and biological evaluation of beta-ketosulfonamide adenylation inhibitors as potential antitubercular agents.
作者信息
Vannada Jagadeshwar, Bennett Eric M, Wilson Daniel J, Boshoff Helena I, Barry Clifton E, Aldrich Courtney C
机构信息
Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
出版信息
Org Lett. 2006 Oct 12;8(21):4707-10. doi: 10.1021/ol0617289.
Abstract
[reaction: see text] The antitubercular nucleoside antibiotics 1 and 2 were recently described that inhibit the adenylate-forming enzyme MbtA and disrupt biosynthesis of the virulence-conferring siderophore known as mycobactin in Mycobacterium tuberculosis. Herein, we report efforts to refine this inhibitor scaffold by replacing the labile acylsulfamate linkage (highlighted) with the more chemically robust beta-ketosulfonamide linkage of 3 and 4.
摘要
[反应：见正文] 抗结核核苷类抗生素1和2最近被报道，它们能抑制腺苷酸形成酶MbtA，并破坏结核分枝杆菌中赋予毒力的铁载体（称为分枝杆菌素）的生物合成。在此，我们报告了通过用3和4中化学性质更稳定的β-酮磺酰胺键取代不稳定的酰基氨基磺酸酯键（突出显示）来优化这种抑制剂支架的研究工作。
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